Biologically active compounds are well known (e.g., aspirin and capsaicin) and have been beneficially administered to patients in need thereof for more than a century. One problem that has been associated with many biologically active compounds is that they can be difficult to dissolve in water or the human body and can also be very difficult to polymerize. Due to the availability and numerous uses of biologically active compounds, it is desirable to enhance their native value by, for example, providing compounds or combinations of compounds with a specific controlled degradation profile or range enabling controlled release of the biologically active compound over an extended, controllable time range.
Polymers prepared from aromatic compounds such as terephthalic acid, p-aminobenzoic acid, and p-phenylenediamine exhibit excellent physical properties, but the polymers are not biodegradable. Polyesters derived from terephthalic acid, such as polyethylene terephthalate (PET), polytrimethylene terephthalate (PTT), and poly(1,4-butylene terephthalate) (PBT) are used extensively for making fibers and molding articles. Some of these are polymers that are used in biomedical applications such as non-absorbable surgical sutures, and these polymers are considered to be safe and biocompatible. Unfortunately, these polymers are non-absorbable and, therefore, cannot be used as absorbable sutures or as absorbable polymers for the controlled release of drugs.
Due to the availability and numerous uses of the polymers derived from these aromatic compounds, it is desirable to enhance their value, for example, by functionalizing these aromatic compounds and preparing absorbable polymers therefrom. The resulting absorbable polymers should have a controlled degradation profile or range enabling controlled release of drugs over an extended, controllable time range when physically admixed with these polymers.
Synthetic absorbable polymers have been used to produce various surgical products such as sutures, implants, prostheses, and the like, for several years. Illustrative U.S. patents describing such polymers include U.S. Pat. Nos. 3,297,033, 3,044,942, 3,371,069, 3,531,561, 3,636,956, Re. 30,170, and 4,052,988.
Polyesters are used routinely by those skilled in the art in various drug delivery systems. For example, U.S. Pat. No. 5,942,252 describes a microcapsule comprising as its biocompatible excipient a poly(lactide-co-glycolide), poly(lactide), poly(glycolide), copolyoxalate, polycaprolactone, poly(lactide-co-caprolactone), poly(esteramide), polyorthoester, poly(p-hydroxybutyric) acid and/or polyanhydride which is disclosed as being useful in delivering antigens or vaccines into and through mucosally-associated lymphoid tissue.
WO 99/29885 describes a process which is disclosed as being useful for degrading poly(ester-amides) and poly(ester-urethanes) encapsulating chemicals, drugs, enzymes, microorganisms and seeds by introducing the polymer to an aqueous nutrient solution and inoculating the solution with a culture containing a selected bacteria.
WO 98/36013 describes aliphatic-aromatic dihydroxy compounds which are disclosed as being useful as controlled drug delivery systems.
WO 97/39738 describes the preparation of microparticles which are disclosed as comprising a sustained release ionic conjugate including a free carboxyl group containing biodegradable polymers and a free amino group-containing drug.
U.S. Pat. No. 5,264,540 describes aromatic polyanhydrides which are disclosed as being biocompatible and biodegradable and which are prepared from para-substituted bis-aromatic dicarboxylic acids for use on wound closure devices. However, these compounds exhibit high melt and glass transition temperatures and decreased solubility, thus making them difficult to process. The disclosed polyanhydrides also comprise radical or aliphatic bonds that cannot be hydrolyzed by water.
Polyanhydride polymeric matrices have also been described for use in orthopedic and dental applications. For example, U.S. Pat. No. 4,886,870 describes an article that is disclosed as being bioerodible and useful for prosthesis and implantation that comprises a biocompatible, hydrophobic polyanhydride matrix. U.S. Pat. No. 5,902,599 describes polymer networks which are formed by polymerizing anhydride prepolymers and which are disclosed as being biodegradable and useful in a variety of dental and orthopedic applications.
It would be desirable to identify methods and compositions for effectively delivering biologically active compounds in a controlled and modifiable fashion. The present invention is directed to these, as well as other important ends.